177Lu-OncoFAP-23 / Philogen - LARVOL DELTA

Effect of molar dose on the in vivo tissue biodistribution profile of FAP-targeted radioligand therapeutics. (PubMed, Eur J Nucl Med Mol Imaging) - "177Lu-OncoFAP-23 presents a favorable in vivo biodistribution profile at molar doses ranging from 90 to 250 nmol/kg in tumor-bearing mice. Our results guide the design of the first-in-human Phase I clinical trial with this novel FAP-targeted radioligand therapeutic."

Journal • Preclinical • Oncology

Preclinical Evaluation of 177Lu-OncoFAP-23, a Multivalent FAP-Targeted Radiopharmaceutical Therapeutic for Solid Tumors. (PubMed, J Nucl Med) - "177Lu-OncoFAP and 177Lu-FAP-2286 were included in the biodistribution study as controls. OncoFAP-23 presents enhanced tumor uptake and tumor retention and low accumulation in healthy organs, findings that correspond to a strongly improved in vivo antitumor efficacy. The data presented in this work support the clinical development of 177Lu-OncoFAP-23 for the treatment of FAP-positive solid tumors."

Journal • Preclinical • Oncology • Solid Tumor • FAP

Tumor-targeted interleukin-2 enhances the anti-cancer activity of multivalent OncoFAP radioligand therapeutics (AACR 2023) - "Moreover, when administered at very low dose 177Lu-OncoFAP-23 exhibited an enhanced anticancer activity compared to a monovalent (177Lu-OncoFAP-DOTAGA) and bivalent (177Lu-BiOncoFAP-DOTAGA) version of OncoFAP. This synergy is driven by NK-cell mediated immune response directed to the tumor, with the concomitant release of granzymes and other pro-apoptotic proteins in the tumor microenvironment. Our findings heighten OncoFAP-based RLTs as promising anti-cancer drugs for treatment of FAP-positive tumors, alone or in combination with targeted interleukin-2."

Oncology • Solid Tumor • FAP • IL2

Philogen Provides Corporate Update (GlobeNewswire) - "¹⁷⁷Lu-OncoFAP-23 is expected to enter in clinical trials by the end of 2023....Authorization from the Italian Medicines Agency, AIFA of the new GMP production facility in Rosia for the production and marketing of drugs is expected in 2023; It should be noted that this new facility will complement the existing GMP plant in Montarioso (Siena), which will be dedicated to the production of investigational drugs."

Commercial • New trial • Oncology

A novel dimeric FAP-targeting small molecule-radio conjugate with high and prolonged tumour uptake (bioRxiv) - "OncoFAP and BiOncoFAP displayed comparable sub-nanomolar dissociation constants towards hFAP in solution, but the bivalent BiOncoFAP bound more avidly to the target immobilized on solid supports. In a comparative biodistribution study, 177Lu-BiOncoFAP exhibited a more stable and prolonged tumour uptake than 177Lu-OncoFAP (~20% ID/g vs ~4% ID/g, at 24h p.i., respectively). Notably, 177Lu-BiOncoFAP showed favorable tumour-to-organ ratios with low kidney uptake. Both 177Lu-OncoFAP and 177Lu-BiOncoFAP displayed potent anti-tumour efficacy when administered at therapeutic doses in tumour bearing mice."

Preclinical • Oncology • Solid Tumor

Philogen Announces Publication of Best-in-Class FAP-Targeting Small Molecule Ligand (OncoFAP) in PNAS (Issuer Direct) - “Philogen…announce a publication describing the development and the in vivo characterization of OncoFAP, a best-in-class FAP-targeting small molecule for applications in cancer and inflammation. The paper entitled ‘An Ultra-High Affinity Small Organic Ligand of Fibroblast Activation Protein for Tumor Targeting Applications’ was published in the peer-reviewed journal PNAS…OncoFAP was further used as modular component for the generation of therapeutic products enabling the targeted delivery of a potent beta-emitter (lutetium-177), of fluorescein-specific CAR T-cells, and of highly cytotoxic auristatin derivatives to FAP-positive tumors in vitro and in vivo.”

Clinical • Oncology • Solid Tumor